Oligiocycloalkanoid Compounds and Methods of Use

Miller etal, US Patent 6,562,782 (May 13, 2003) Assignee University of Rochester Utility Drug Delivering Agent 

Norbornylene was dissolved in a 1 1 solution of t-butyl alcohol and an oxidant mixture consisting of K3Ee(CN)6, K2CO3, CH3SO2NH2, quinuclidine and K2OSO4 H2O added. The product was isolated and used directly thereafter (Note 1). 

The product from the Step 1 was dissolved in a 3 1 mixture of THF and water and NaI04 added at 0°C. The mixture reacted 12 hours while gradually warming to ambient temperature. The product was purified by flash filtration and isolated in 57% yield. 

Lithium aluminum hydride (96.24 mmol) was slurried into 130 ml THF at ambient temperature and the product from Step 4 (16.04 mmol) dissolved in 30 ml THF added over 15 minutes. Thereafter, the mixture stirred 3 hours, was quenched sequentially with 3.6 ml water, 3.6 ml 15% NaOH, 15 ml water, and the contents stirred for 2 hours. The mixture was filtered through celite and the filtrate concentrated to a yellow oil. The product was isolated by flash chromatography on silica using hexanes/EtOAc, 66 34 in 53% yield. 

The product from Step 5 (9.85 mmol) was slurried to form a 0.2 M solution in CH2CI2 whereupon benzoyl chloride (35.7 mmol) and EtjN (39.36 mmol) were added and the reaction stirred 4 hours. The reaction was quenched with 25 ml water and then poured into 100 ml diethyl ether. The organic layer was washed twice with 100 ml apiece water, buffered aqueous solution of H2PO4 H20/concentrated HCl having a pH = 2, Na2C03, and 100 ml brine. The product was isolated by the method of Step 4 in 91% yield. 

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